Type I interferon gene therapy protects against cytomegalovirus-induced myocarditis
Type I interferon gene therapy protects against cytomegalovirus-induced myocarditis
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DOI：
10.1046/j.1365-2567.2002.01423.x
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发表时间：
2002-07-01
期刊：
影响因子：
6.4
通讯作者：
James, CM
中科院分区：
文献类型：
--
作者：
Cull, VS;Bartlett, EJ;James, CM
I型干扰素（IFN）在对病毒感染的早期应答中产生并调节适应性免疫。以前，我们证明了对小鼠巨细胞病毒（MCMV）感染IFN DNA接种小鼠的局部保护。在这里，我们研究了七种IFN亚型（IFNA 1，A2，A4，A5，A6，A9和B），通过DNA接种给药，对系统性MCMV感染和心肌炎的影响。IFN转基因表达改变了MCMV感染的病毒滴度和心肌炎的发病机制。IFNA 6处理减少MCMV复制，而IFNA 5和A2增强病毒复制。IFN-α 6、A9和B处理抑制急性心肌炎。辅助性T细胞1型样抗体和细胞因子反应与病毒滴度降低和心肌炎相关。此外，IFNA 6能够减少慢性心脏炎症。这项研究对七种I型干扰素的有效性进行了研究，使用DNA基因治疗，强调了在疾病治疗中正确使用亚型的必要性。我们证明了有效的亚型治疗急性和慢性阶段的MCMV感染和由此产生的心肌炎的发展。
Type I interferons (IFNs) are produced early in response to viral infection and modulate adaptive immunity. Previously we demonstrated localized protection against murine cytomegalovirus (MCMV) infection in IFN DNA-inoculated mice. Here we examine the effect of seven IFN subtypes (IFNA1 , A2 , A4 , A5 , A6 , A9 and B ), administered by DNA inoculation, on systemic MCMV infection and myocarditis. IFN transgene expression altered the pathogenesis of MCMV infection with regard to virus titre and myocarditis. IFNA6 treatment reduced MCMV replication whilst IFNA5 and A2 enhanced virus replication. IFNA6 , A9 , and B treatment inhibited acute myocarditis. A T helper type 1-like, antibody and cytokine, response correlated with decreased virus titre and myocarditis. In addition, IFNA6 was able to reduce chronic cardiac inflammation. This research into the effectiveness of seven type I IFNs, using DNA gene therapy, highlights the need for correct subtype usage in the treatment of disease. We demonstrate effective subtypes for treatment in both the acute and chronic phases of MCMV infection and the resultant development of myocarditis.